title: A randomized controlled trial investigation of a non-stimulant in attention deficit hyperactivity disorder (ACTION): rationale and design.
abstract: BACKGROUND
  The ACTION study (Attention deficit hyperactivity disorder Controlled Trial Investigation Of a Non-stimulant) is a multi-center, double-blind, randomized cross-over trial of the non-stimulant medication, Atomoxetine, in children and adolescents with attention deficit hyperactivity disorder (ADHD). The primary aims are to examine the efficacy of atomoxetine for improving cognition and emotional function in ADHD and whether any improvements in these outcomes are more pronounced in participants with comorbid anxiety; and to determine if changes in these outcomes after atomoxetine are more reliable than changes in diagnostic symptoms of ADHD. This manuscript will describe the methodology and rationale for the ACTION study.
  
  
  METHODS
  Children and adolescents aged 6 - 17 y with ADHD will be enrolled. Clinical interview and validated scales will be used to confirm diagnosis and screen for exclusion criteria, which include concurrent stimulant use, and comorbid psychiatric or neurological conditions other than anxiety. Three assessment sessions will be conducted over the 13-week study period: Session 1 (Baseline, pre-treatment), Session 2 (six weeks, atomoxetine or placebo), and Session 3 (13 weeks, cross-over after one-week washout period). The standardized touch-screen battery, "IntegNeuro™", will be used to assess cognitive and emotional function. The primary measure of response will be symptom ratings, while quality of life will be a secondary outcome. Logistic regression will be used to determine predictors of treatment response, while repeated measures of analysis will determine any differences in effect of atomoxetine and placebo.
  
  
  RESULTS
  The methodology for the ACTION study has been detailed.
  
  
  CONCLUSIONS
  The ACTION study is the first controlled trial to investigate the efficacy of atomoxetine using objective cognitive and emotional function markers, and whether these objective measures predict outcomes with atomoxetine in ADHD with and without comorbid anxiety. First enrollment was in March 2008. The outcomes of this study will be a significant step towards a 'personalized medicine' (and therefore a more efficient) approach to ADHD treatment.
  
  
  BACKGROUND
  Australian and New Zealand Clinical Trials Registry ANZCTRN12607000535471.
authors.affiliation: Brain Dynamics Centre, Sydney Medical School and Westmead Millennium Institute, Sydney, New South Wales, Australia. tracey.tsang@sydney.edu.au
authors.forename: Tracey W
authors.initials: TW
authors.lastname: Tsang
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kohn
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hermens
authors.forename: Simon D
authors.initials: SD
authors.lastname: Clarke
authors.forename: C Richard
authors.initials: CR
authors.lastname: Clark
authors.forename: Daryl
authors.initials: D
authors.lastname: Efron
authors.forename: Noel
authors.initials: N
authors.lastname: Cranswick
authors.forename: Chris
authors.initials: C
authors.lastname: Lamb
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Williams
mesh_terms: D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use*; D000339:Affect; D001007:Anxiety / Q000453:epidemiology; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000523:psychology; D001315:Australia / Q000453:epidemiology; D002648:Child; D003071:Cognition; D015897:Comorbidity; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D016015:Logistic Models; D009483:Neuropsychological Tests; D011437:Propylamines / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012107:Research Design; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018759:Adrenergic Uptake Inhibitors; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride